Application of the activated sludge model for nitrogen to elevated nitrogen conditions.
The Activated Sludge Model for Nitrogen (ASMN) was evaluated by conducting simulations under both steady-state and dynamic conditions using a wastewater containing high concentrations of chemical oxygen demand (COD) and nitrogen, and an inhibitor of ammonia-oxidizing bacteria. The adopted wastewater characteristics were based on data from several industrial wastewater treatment facilities. The simulations were performed at a variety of temperatures, solids retention times, dissolved oxygen concentrations, pH values, and salt concentrations. The nitrification operating window was defined, and denitrification performance was characterized. The pH and temperature were found to be the most important variables affecting nitrification performance under upset or startup conditions, with lower pH values allowing better performance at higher temperatures for the high-nitrogen wastewater used in the simulations. Emissions of nitric oxide and nitrous oxide were higher than generally thought to occur and were directly linked to depletion of the electron donor in the anoxic reactor. The findings concerning pH, temperature, and gaseous emissions were all consistent with the known growth characteristics of nitrifying and denitrifying bacteria. Parameter and process variable sensitivity studies were performed, and guidelines for improved biological nitrogen removal were developed.


Anticonvulsant osteomalacia.
Drug-induced osteomalacia appears to be a relatively common disorder in patients receiving long-term anticonvulsant drug therapy. The severity of clinical manifestations in any given individual appears to be a function of the combined effects of a variety of factors including drug type and total drug dose, dietary vitamin D intake, sunlight exposure, and physical activity level. Aided by the recent development of sensitive techniques such as the serum 25-hydroxyvitamin D assay and the photon absorption methods for bone mass determination, one can now detect abnormalities in vitamin D and bone metabolism with much greater precision. As a consequence, the incidence of disordered mineral metabolism in patients receiving long-term anti-convulsant therapy can be determined with greater precision and therapeutic regimens instituted to prevent the associated morbidity.


Comparison of sunlight-AOPs for levofloxacin removal: kinetics, transformation products, and toxicity assay on Escherichia coli and Micrococcus flavus.
Levofloxacin (LFX) is a widely used antibiotic medication. Persistent traces of LFX in water and wastewater may induce bacterial resistance. Photon-driven advanced oxidation processes (AOPs) can assist in attaining complete abatement of LFX for environmental protection. This work benchmarks different solar AOPs based on hydroxyl radical (OH•) and sulphate radical (SO4•-) chemistry. Other oxidant precursors, as radical sources, were used to selectively control the generation of either hydroxyl radical (i.e., H2O2), sulphate radical (i.e., peroxydisulphate (PDS)), or a controlled mixture ratio of both OH•/SO4•- (i.e., peroxymonosulphate (PMS)). The influence of pH on degradation performance was evaluated using unbuffered and buffered solutions. Simulated irradiation/PMS process exhibited a strong pH-dependence attaining partial degradation of ca. 56% at pH 5 up to complete degradation at pH 7. Despite the similitudes on the abatement of target pollutant LFX in pristine solutions, only simulated irradiation/PDS treatment achieved effective abatement of LFX in wastewater samples given the higher selectivity of SO4•-. Toxicity tests were conducted with Escherichia coli (LMG2092) and Micrococcus flavus (DSM1790), demonstrating successful inhibition of the antibiotic character of polluted waters, which would contribute to preventing the development of resistant bacterial strains. Finally, a degradative pathway was suggested from the by-products and intermediates identified by LC-MS. Results demonstrate that the degradation of specific functional groups (i.e., piperazine ring) is associated with the loss of antibacterial character of the molecule.


A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.
The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content.


Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation.
Acute stress impairs memory retrieval of several types of memories. An increase in glucocorticoids, several minutes after stressful events, is described as essential to the impairing retrieval-effects of stressors. Moreover, memory retrieval under stress can have long-term consequences. Through what process does the reactivated memory under stress, despite the disrupting retrieval effects, modify long-term memories? The reconsolidation hypothesis proposes that a previously consolidated memory reactivated by a reminder enters a vulnerability phase (labilization) during which it is transiently sensitive to modulation, followed by a re-stabilization phase. However, previous studies show that the expression of memories during reminder sessions is not a condition to trigger the reconsolidation process since unexpressed memories can be reactivated and labilized. Here we evaluate whether it is possible to reactivate-labilize a memory under the impairing-effects of a mild stressor. We used a paradigm of human declarative memory whose reminder structure allows us to differentiate between a reactivated-labile memory state and a reactivated but non-labile state. Subjects memorized a list of five cue-syllables associated with their respective response-syllables. Seventy-two hours later, results showed that the retrieval of the paired-associate memory was impaired when tested 20min after a mild stressor (cold pressor stress (CPS)) administration, coincident with cortisol levels increase. Then, we investigated the long-term effects of CPS administration prior to the reminder session. Under conditions where the reminder initiates the reconsolidation process, CPS impaired the long-term memory expression tested 24h later. In contrast, CPS did not show effects when administered before a reminder session that does not trigger reconsolidation. Results showed that memory reactivation-labilization occurs even when retrieval was impaired. Memory reactivation under stress could hinder -via reconsolidation- the probability of the traces to be expressed in the long term.


Factors influencing hospital foodservice staff's capacity to deliver a nutrition intervention.
Implementation of an intervention can result in a discrepancy between what was planned and what is delivered, affecting outcomes for recipients. The aim was to explore, from the perspective of hospital foodservice staff, their experiences delivering a nutrition intervention and the barriers and enablers to its implementation. A process evaluation of a pilot study was undertaken using qualitative description. A purposive sample (n = 15) of hospital foodservice supervisors and foodservice assistants responsible for delivering a higher energy menu to hospital patients participated in focus groups and semistructured interviews. Theoretical frameworks of behaviour underpinned the method. Content analysis elicited factors (sub-themes) influencing foodservice staff's capability, opportunity and motivation to provide the nutrition intervention. Thematic analysis (by two independent researchers) further explored factors (themes) related to the process of the intervention's implementation. Five key themes (and 15 sub-themes) explained factors effecting implementation of the nutrition intervention. Aspects of the foodservice environment and patients' resistance were barriers to implementation and perceived sustainability. Teamwork, problem solving, leadership and job satisfaction were enablers. There was an opportunity to optimise training and feedback. Characteristics of foodservice staff, including their: knowledge, beliefs and perceptions of diet, health and their job role, had the potential to influence their behaviours and decision making. A number of interacting factors influenced foodservice staff's delivery of a higher energy menu as planned. Addressing the challenges of time, foodservice structure, patients' resistance, gaps in knowledge and misconceptions among foodservice staff may enhance similar nutrition interventions in the future.


Neurotrophin 3 induces structural and functional modification of synapses through distinct molecular mechanisms.
The mechanisms by which neurotrophins elicit long-term structural and functional changes of synapses are not known. We report the mechanistic separation of functional and structural synaptic regulation by neurotrophin 3 (NT-3), using the neuromuscular synapse as a model. Inhibition of cAMP response element (CRE)-binding protein (CREB)-mediated transcription blocks the enhancement of transmitter release elicited by NT-3, without affecting the synaptic varicosity of the presynaptic terminals. Further analysis indicates that CREB is activated through Ca(2+)/calmodulin-dependent kinase IV (CaMKIV) pathway, rather than the mitogen-activated protein kinase (MAPK) or cAMP pathway. In contrast, inhibition of MAPK prevents the NT-3-induced structural, but not functional, changes. Genetic and imaging experiments indicate that the small GTPase Rap1, but not Ras, acts upstream of MAPK activation by NT-3. Thus, NT-3 initiates parallel structural and functional modifications of synapses through the Rap1-MAPK and CaMKIV-CREB pathways, respectively. These findings may have implications in the general mechanisms of long-term synaptic modulation by neurotrophins.


SOS induction in Escherichia coli and Salmonella mutagenicity: a comparison using 330 compounds.
To examine the concordance of two microbial genotoxicity short-term assays, 330 experimental results for the SOS chromotest using tester strain Escherichia coli PQ37 were compared with the results of the Salmonella/mammalian microsome mutagenicity assay with Salmonella typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and/or TA1538. With respect to qualitative features, the concordance between SOS chromotest and Salmonella mutagenicity test results was 86.4% (sensitivity, 78.6%; specificity, 100%; chi 2 = 188.6). None of the non-mutagens (N = 120) were able to induce the SOS system. Additionally, 45 of the 210 S.typhimurium mutagens (21.5%) did not induce the SOS repair system. On closer examination, the majority of these 45 compounds (84%) were mutagens with activities between 0.001 and 10 rev/nmol. Even though the experimental protocols of both systems were not standardized, the correlation coefficient for the experimental results of the two test systems was 0.7 for the 330 chemicals. Except for aliphatic epoxides (r = 0.47), the mutagenicity/SOS induction correlations for congeneric data sets (polycyclic aromatic hydrocarbons, nitroarenes, nitroarenofurans, mycotins) were even better (r = 0.72-0.95). Additionally, computer automated structure evaluation (CASE) analyses of the nature of the structural determinants associated with each endpoint indicate extensive homologies. The data can be taken to indicate that the two phenomena reflect common mechanisms of action.


Use of UV-C treatments to maintain quality and extend the shelf life of green fresh-cut bell pepper (Capsicum annuum L.).
The objective of this work was to select a Ultraviolet-C (UV-C) treatment for fresh-cut mature green bell pepper, and to evaluate the effect of its combination with refrigeration on quality maintenance. Bell pepper sticks were treated with 0, 3, 10, or 20 kJ/m² UV-C in the outer (O), inner (I), or both sides of the pericarp (I/O) and stored for 8 d at 10 °C. During the first 5 d of storage, all UV-C treatments reduced deterioration as compared to the control. The treatment with 20 kJ/m² I/O was the most effective to reduce deterioration, and was used for further evaluations. In a second group of experiments, mature green bell pepper sticks were treated with 20 kJ/m² I/O, stored at 5 °C for 7 or 12 d and assessed for physical and chemical analysis, and microbiological quality. UV-C-treated fruit showed lower exudates and shriveling than the control. UV exposure also reduced decay, tissue damage, and electrolyte leakage. After 12 d at 5 °C, UV-C irradiated peppers remained firmer and had higher resistance to deformation than the control. The UV-C treatments also reduced weight loss and pectin solubilization. UV-C exposure decreased the counts of mesophile bacteria and molds, and did not affect acidity or sugars. UV-C-treated fruit stored for 0 or 7 d at 5 °C did not show major differences in antioxidants from the control as measured against DPPH(•) or ABTS(•)⁺ radicals. Results suggest that UV-C exposure is useful to maintain quality of refrigerated fresh-cut green pepper. Exposure to UV-C radiation before packing and refrigeration could be a useful nonchemical alternative to maintain quality and reduce postharvest losses in the fresh-cut industry.


Proteomes: A New Proteomic Journal.
In the early years of proteomics, mass spectrometry served only as a technique in protein chemistry facilitating the characterization of purified proteins and mapping their posttranslational modifications (PTMs). A bit later this technique almost completely replaced Edman degradation and amino acid analysis. The continuous development of the mass spectrometry techniques created a huge analytical potential allowing the study of nearly complete proteomes in single experiments. This evolution distanced proteomics from protein chemistry and placed it in a novel position. Its capability to identify and quantify in parallel thousands of proteins and their modifications at minute sample amount requirements is one of the most fascinating technological advances in biology today. [...].


Antimicrobial resistance of Staphylococcus pseudintermedius.
Staphylococcus pseudintermedius, Staphylococcus intermedius and Staphylococcus delphini together comprise the S. intermedius group (SIG). Within the SIG, S. pseudintermedius represents the major pathogenic species and is involved in a wide variety of infections, mainly in dogs, but to a lesser degree also in other animal species and humans. Antimicrobial agents are commonly applied to control S. pseudintermedius infections; however, during recent years S. pseudintermedius isolates have been identified that are meticillin-resistant and have also proved to be resistant to most of the antimicrobial agents approved for veterinary applications. This review deals with the genetic basis of antimicrobial resistance properties in S. pseudintermedius and other SIG members. A summary of the known resistance genes and their association with mobile genetic elements is given, as well as an update of the known resistance-mediating mutations. These data show that, in contrast to other staphylococcal species, S. pseudintermedius seems to prefer transposon-borne resistance genes, which are then incorporated into the chromosomal DNA, over plasmid-located resistance genes.


PulseRider Treated Aneurysm with Significant Artifact on Postoperative Magnetic Resonance Angiography: A Case Report and Literature Review.
The PulseRider is a neuroendovascular adjunct for wide-necked intracranial aneurysms. The decreased metal burden of the PulseRider theoretically reduces artifact on radiologic imaging. However, we report here on a case of a patient who underwent PulseRider-assisted stent-coiling of a basilar tip aneurysm. He returned 19 months later for intermittent diplopia and darkening of vision but was neurologically intact on exam. Both contrast-enhanced and time-of-flight magnetic resonance angiography (MRA) demonstrated absence of signal in the basilar artery in the proximal anchors of the PulseRider. Given his lack of reproducible symptoms and high functional status, it is presumed that the imaging reflected artifact and not thrombosis/stenosis. Although the PulseRider is a useful treatment option for wide-necked intracranial aneurysms, the clinician should be aware that even contrast-enhanced MRA can produce artifact that resembles thrombosis/stenosis. Non-angiogram radiologic imaging modalities may be appropriate for evaluation for residual aneurysm but not patency of the parent artery.


Preferences for oral fluid rapid HIV self-testing among social media-using young black, Hispanic, and white men-who-have-sex-with-men (YMSM): implications for future interventions.
We assessed preferences of social media-using young black, Hispanic and white men-who-have-sex-with-men (YMSM) for oral fluid rapid HIV self-testing, as compared to other currently available HIV testing options. We also identified aspects of the oral fluid rapid HIV self-test that might influence preferences for using this test instead of other HIV testing options and determined if consideration of HIV testing costs and the potential future availability of fingerstick rapid HIV self-testing change HIV testing preferences. Anonymous online survey. HIV-uninfected YMSM across the United States recruited from multiple social media platforms completed an online survey about willingness to use, opinions about and their preferences for using oral fluid rapid HIV self-testing and five other currently available HIV testing options. In a pre/post questionnaire format design, participants first indicated their preferences for using the six HIV testing options (pre) before answering questions that asked their experience with and opinions about HIV testing. Although not revealed to participants and not apparent in the phrasing of the questions or responses, the opinion questions concerned aspects of oral fluid rapid HIV self-testing (e.g. its possible advantages/disadvantages, merits/demerits, and barriers/facilitators). Afterward, participants were queried again about their HIV testing preferences (post). After completing these questions, participants were asked to re-indicate their HIV testing preferences when considering they had to pay for HIV testing and if fingerstick blood sample rapid HIV self-testing were an additional testing option. Aspects about the oral fluid rapid HIV self-test associated with increased preference for using the test (post-assessment vs pre-assessment of opinion topics) were identified through multivariable regression models that adjusted for participant characteristics. Of the 1975 YMSM participants, the median age was 22 years (IQR 20-23); 19% were black, 36% Hispanic, and 45% white; and 18% previously used an oral fluid rapid HIV self-test. Although views about oral fluid rapid HIV self-testing test were favorable, few intended to use the test. Aspects about the oral fluid rapid HIV self-test associated with an increased preference for using the test were its privacy features, that it motivated getting tested more often or as soon as possible, and that it conferred feelings of more control over one's sexual health. Preferences for the oral fluid rapid HIV self-test were lower when costs were considered, yet these YMSM were much more interested in fingerstick blood sampling than oral fluid sampling rapid HIV self-testing. Despite the perceived advantages of the oral fluid rapid HIV self-test and favorable views about it by this population, prior use as well as future intention in using the test were low. Aspects about oral fluid rapid HIV self-testing identified as influential in this study might assist in interventions aimed to increase its use among this high HIV risk population as a means of encouraging regular HIV testing, identifying HIV-infected persons, and linking them to care. Although not yet commercially available in the United States, fingerstick rapid HIV self-testing might help motivate YMSM to be tested more than oral fluid rapid HIV self-testing.


Are things really so different? A research finding of satisfaction, illness and depression in rural South African elderly.
This study was conducted as a part of a larger study to create a database to describe elderly respondents residing in a rural South African community. The participants reported on their perceptions of social support, satisfaction, and illness in relationship to depression. There was a correlation between social support and satisfaction (r = .048502, p = .0001). Depression was not found to be a significant health problem in this elderly population. However, there were correlations between hypertension and depression noted (r = .57901, p = .0001).


TestisBank: an internet-based gene sequence database of the testis.
The testis is a highly transcriptionally active organ with hundreds of genes expressed during different stages of spermatogenesis. Scientists working on the testis are restricted to using two sources for further information on testicular genes, GenBank and MEDLINE. However, these two databases are not completely linked and give only very little information on the cellular type of expression or whether a gene is cloned in other tissues but is also expressed in the testis. We have generated an organ-specific database named TestisBank, which is capable of retrieving a more complete set of genes expressed in the different cell types of the testis. Furthermore, it extends to the epididymis which plays an important role in germ cell maturation. TestisBank is automatically updated to match the current status of sequence entries in the genome databases and it provides the user with an interface convenient to handle and provides useful links related to male reproduction. The TestisBank is publicly available at http://medweb.uni-muenster.de/TestisBank/. The design of the TestisBank may provide a simple model for the development of databases in which molecular and literature data are merged, thereby allowing detailed insight into the contribution of different cells/genes to the complex process of spermatogenesis.


Arsenic disruption of steroid receptor gene activation: Complex dose-response effects are shared by several steroid receptors.
Chronic intake of arsenic (As) has been associated with increased risk of cancer, diabetes, developmental and reproductive problems, and cardiovascular disease. Recent studies suggest increased health risks with drinking water levels as low as 5-10 ppb. We previously reported that As disrupts glucocorticoid receptor (GR) mediated transcription in a very complex fashion. Low As levels (0.1-0.7 microM) stimulated transcription, whereas slightly higher levels (1-3 microM) were inhibitory. The DNA binding domain (DBD) was the minimal region of GR required for the response to As. Mutations in the DBD that alter the conformation of the dimerization domain (D-loop) to a DNA-bound GR conformation abolished the stimulatory effect and enhanced the inhibitory response to As. Here we report that receptors for progesterone (PR) and mineralocorticoids display a complex As response similar to that of the GR, suggesting a common mechanism for this effect. The complex response to As is not due to altered steroid or receptor levels. Moreover, a well-characterized GR dimerization mutant displayed a wild-type biphasic response to As for several divergent reporter genes, suggesting that dimerization is not critical for the response to As. Fluorescence polarization studies with purified PR and GR demonstrated that the specific PR/GR-DNA interaction is not altered in the presence of As. These results indicate that the numerous and diverse human health effects associated with As exposure may be mediated, at least in part, through its ability to simultaneously disrupt multiple hormone receptor systems.


A Methylcellulose Hydrogel as Support for 3D Plotting of Complex Shaped Calcium Phosphate Scaffolds.
3D plotting is an additive manufacturing technology enabling biofabrication, thus the integration of cells or biologically sensitive proteins or growth factors into the manufacturing process. However, most (bio-)inks developed for 3D plotting were not shown to be processed into clinically relevant geometries comprising critical overhangs and cavities, which would collapse without a sufficient support material. Herein, we have developed a support hydrogel ink based on methylcellulose (mc), which is able to act as support as long as the co-plotted main structure is not stable. Therefore, 6 w/v %, 8 w/v % and 10 w/v % mc were allowed to swell in water, resulting in viscous inks, which were characterized for their rheological and extrusion properties. The successful usage of 10 w/v % mc as support ink was proven by multichannel plotting of the support together with a plottable calcium phosphate cement (CPC) acting as main structure. CPC scaffolds displaying critical overhangs or a large central cavity could be plotted accurately with the newly developed mc support ink. The dissolution properties of mc allowed complete removal of the gel without residuals, once CPC setting was finished. Finally, we fabricated a scaphoid bone model by computed tomography data acquisition and co-extrusion of CPC and the mc support hydrogel.


Women's Experiences of Health-Related Communicative Disenfranchisement.
Women's inequitable healthcare experiences are epistemic injustices by which women are discredited and harmed in their position as knowers of their health and their bodies. Drawing on the theory of communicative disenfranchisement (TCD), we sought to amplify voices of women experiencing communicative disenfranchisement (CD) and to unify their stories according to theoretical premises, namely, attention to power, material conditions, discourse, identities and relationships, and process. We interviewed 36 women living in the United States whose health issues have not been taken seriously by health care providers, friends, and family - pervasive sources of disenfranchising talk surrounding health. Mapping onto the TCD framework, our findings explicate the process of CD, including the material and immaterial consequences of disenfranchising talk and women's responses to such talk. CD unfolded as a protracted and often circular process of women seeking care but encountering health dismissals and minimalizations, blaming and shaming, normalizing of their pain, and psychologizing. We unpack how disenfranchising talk rendered women crazy and dehumanized them and inflicted shame and loss. Women responded to disenfranchising talk with silence, and they (re)claimed their voice by resisting psychogenic explanations for their problems, critiquing women's healthcare, asserting their needs, and advocating for others. We discuss the implications of this research for theory and praxis.


The Clinician's Toolbox: Assessing the Sexual Impacts of Cancer on Adolescents and Young Adults with Cancer (AYAC).
Adolescents and young adults aged 15-39 years who have been diagnosed with cancer (AYAC) have unique medical and psychosocial needs. Following their cancer treatments, AYAC must learn to manage the sometimes irreversible general side effects of cancer treatments including side effects that impact their sexuality. These side effects include but are not limited to: infertility, altered body/physical appearance, and sexual dysfunction. Such effects may hinder AYAC efforts to date and experiment sexually, limiting sexual maturation and confidence, as well as the formation or maintenance of meaningful couple and sexual relationships. It is clear that we need to tailor our clinical approaches to ensure that we assess the unique needs and concerns faced by AYAC. Based on consistent study findings substantiating the distinctive needs of AYAC, the main objective of this article is to present the core clinical components involved in assessing sexuality among AYAC. The clinical recommendations are based on the authors and experts' clinical experiences coupled with a thorough examination of the literature related to AYAC sexuality. This article first describes the three components (clinical interview, review of chart notes, and self-report questionnaires) of a sexuality assessment and the seven core domains that highlight target areas of focus. A detailed outline of each of the core domains of assessment (socio-demographics; medical history; fertility and sexually transmitted infection; sexual functioning; sexual coping style; body and self-image; and sexual history and dating/couple experience) is presented. A "toolbox" table containing useful resources for clinicians (e.g., questionnaires and red flags) and direct resources for AYAC patients are included. Cancer can have a significant impact on numerous domains of AYAC sexuality. The assessment of and attention to the impact of sexuality on AYAC is crucial in order to provide effective and comprehensive quality patient cancer care.


Lumbar radicular pain.
Radicular pain is caused by irritation of the sensory root or dorsal root ganglion of a spinal nerve. The irritation causes ectopic nerve impulses perceived as pain in the distribution of the axon. The pathophysiology is more than just mass effect: it is a combination of compression sensitising the nerve root to mechanical stimulation, stretching, and a chemically mediated noncellular inflammatory reaction. This article discusses the clinical features, assessment and management of lumbar radicular pain (LRP). Lumbar radicular pain is sharp, shooting or lancinating, and is typically felt as a narrow band of pain down the length of the leg, both superficially and deep. It may be associated with radiculopathy (objective sensory and/or motor dysfunction as a result of conduction block) and may coexist with spinal or somatic referred pain. In more than 50% of cases, LRP settles with simple analgesics. Significant and lasting pain relief can be achieved with transforaminal epidural steroid injection. Surgery is indicated for those patients with progressive neurological deficits or severe LRP refractory to conservative measures.


Secondary metabolites from fungus Nigrospora sp.
Six compounds were purified from the extracts of fungus Z18-17 (Nigrospora sp.) isolated from Scyphiphora hydrophyllacea, a tree from the intertidal zone of Shankou, Guangxi Province of China, which was reported to have cytotoxic activity. Systematic study on the chemical constituents of Nigrospora sp. resulted in the isolation of one new 6-phenylhexanoic acid derivative, one new derivative of uridine, and four known compounds. Their structures were characterized, respectively, as methyl 5-acetamido-6-(4-hydroxyphenyl)-4-oxohexanoate (1), uridine-5'α-hydroxypropanoate (2), 4-hydroxyphenethyl 2-hydroxypropanoate (3), methyl pyroglutamate (4), cyclo (Pro-Val) (5), and cyclo (Phe-Hyp) (6). The cytotoxic activities of the two new compounds against HL-60 cell line were tested and the IC(50) values of the two new compounds were all over 100 μM.


Toxicity of excipients--a Food and Drug Administration perspective.
Excipients are essential components of drug products. They are also potential toxicants. Examples of known excipient-induced toxicities include renal failure and death from diethylene glycol, osmotic diarrhea caused by ingested mannitol, hypersensitivity reactions from lanolin, and cardiotoxicity induced by propylene glycol. Proposals to test or market new drug products in the United States should adequately address the safety of the proposed exposure to the excipients in those products. The specific safety data that may be needed will vary depending upon the clinical situation, including such factors as the duration, level, and route of exposure, but may include acute, repeat-dose, reproductive, and genetic toxicity data, carcinogenicity data, and specialized toxicology information, such as sensitization or local irritation data. Many guidances exist to aid in the development of pharmaceuticals, including the International Conference on Harmonization (ICH) documents and various Food and Drug Administration/Center for Drug Evaluation and Research (FDA/CDER) pharmacology and toxicology guidances. The FDA/CDER has recently adopted a new guidance for industry, "Nonclinical Studies for Development of Pharmaceutical Excipients," which focuses on issues associated with development of safety databases that will support clinical use of excipients in drug products. The new guidance document is introduced and discussed in this article.


Identification of differentially regulated micrornas in cold-hardy insects.
Freeze tolerance in insects is associated with cryoprotectant synthesis and strong metabolic suppression. Freeze avoidance, an alternative strategy in cold-hardy insects, is also characterized by hypometabolism, but possesses significant cellular and physiological differences when compared with freeze tolerance. We hypothesized that microRNAs, non-coding transcripts that bind to mRNA, could play a role in the regulation of energy-expensive mRNA translation in insects exposed to low temperatures. Expression levels of microRNA species were evaluated during cold acclimation of freeze tolerant Eurosta solidaginis and freeze-avoiding Epiblema scudderiana, comparing control (5 degree C) conditions with larvae given sequential exposures to -5 degree C and -15 degree C. MiR-1 levels were significantly elevated in frozen E. solidaginis larvae at -15 degree C, whereas miR-34 levels were unchanged. MiR-1 and miR-34 levels remained stable in E. scudderiana. These data demonstrate differential microRNA expression in frozen versus control insect larvae and highlight contrasting microRNA signatures between freeze tolerant and freeze avoiding species.


Electromagnetic Differential Measuring Method: Application in Microstrip Sensors Developing.
Electromagnetic radiation is energy that interacts with matter. The interaction process is of great importance to the sensing applications that characterize material media. Parameters like constant dielectric represent matter characteristics and they are identified using emission, interaction and reception of electromagnetic radiation in adapted environmental conditions. How the electromagnetic wave responds when it interacts with the material media depends on the range of frequency used and the medium parameters. Different disciplines use this interaction and provides non-intrusive applications with clear benefits, remote sensing, earth sciences (geology, atmosphere, hydrosphere), biological or medical disciplines use this interaction and provides non-intrusive applications with clear benefits. Electromagnetic waves are transmitted and analyzed in the receiver to determine the interaction produced. In this work a method based in differential measurement technique is proposed as a novel way of detecting and characterizing electromagnetic matter characteristics using sensors based on a microstrip patch. The experimental results, based on simulations, show that it is possible to obtain benefits from the behavior of the wave-medium interaction using differential measurement on reception of electromagnetic waves at different frequencies or environmental conditions. Differential method introduce advantages in measure processes and promote new sensors development. A new microstrip sensor that uses differential time measures is proposed to show the possibilities of this method.


The morphogenesis of the vacuolation of liver cells.
The morphogenesis of the vacuolation of liver cells caused by congestion was studied in the rat. Congestion of the liver was produced by constriction of the inferior vena cava just below the diaphragm. Vacuoles appeared within 5 min after the constriction (inferior vena cava pressure: 50 mm H2O or more). Vacuolation began as a small and saccular invagination of the sinusoidal surface of the liver cell membrane, and at the initial stage the vacuolar lumen connected with the space of Disse through a narrow slit. The small vacuoles increased in size and became larger by fusing with each other. The limiting membrane of vacuoles showed identical enzymological activities to those in the liver cell membrane. Vacuoles contained some components of blood and horseradish peroxidase injected into the femoral vein. These findings suggest that vacuolation of liver cells is formed by invaginations of liver cell membrane.


Over-expression of an Na+-and K+-permeable HKT transporter in barley improves salt tolerance.
Soil salinity is an increasing menace that affects agriculture across the globe. Plant adaptation to high salt concentrations involves integrated functions, including control of Na+ uptake, translocation and compartmentalization. Na+ transporters belonging to the HKT family have been shown to be involved in tolerance to mild salt stress in glycophytes such as Arabidopsis, wheat and rice by contributing to Na+ exclusion from aerial tissues. Here, we have analysed the role of the HKT transporter HKT2;1, which is permeable to K+ and Na+, in barley, a relatively salt-tolerant crop that displays a salt-including behaviour. In Xenopus oocytes, HvHKT2;1 co-transports Na+ and K+ over a large range of concentrations, displaying low affinity for Na+, variable affinity for K+ depending on external Na+ concentration, and inhibition by K+ (K(i) approximately 5 mm). HvHKT2;1 is predominantly expressed in the root cortex. Transcript levels are up-regulated in both roots and shoots by low K+ growth conditions, and in shoots by high Na+ growth conditions. Over-expression of HvHKT2;1 led to enhanced Na+ uptake, higher Na+ concentrations in the xylem sap, and enhanced translocation of Na+ to leaves when plants were grown in the presence of 50 or 100 mm NaCl. Interestingly, these responses were correlated with increased barley salt tolerance. This suggests that one of the factors that limits barley salt tolerance is the capacity to translocate Na+ to the shoot rather than accumulation or compartmentalization of this cation in leaf tissues. Thus, over-expression of HvHKT2;1 leads to increased salt tolerance by reinforcing the salt-including behaviour of barley.


Antifibrogenic effects of liposome-encapsulated IFN-alpha2b cream on skin wounds in a fibrotic rabbit ear model.
This study was conducted to assess the ability of a dermal cream containing liposome-encapsulated interferon- alpha2b (IFN-alpha2b) (LIPO+IFN) to improve hypertrophic scarring in open and reepithelialized dermal wounds in a rabbit fibrotic ear model. Full-thickness skin wounds were made in New Zealand white rabbits, and were either left untreated, treated on day 16 postsurgery (open wound), or treated on day 23 postsurgery (reepithelialized wound) with either LIPO+IFN or liposome alone (LIPO). The conditions of the wounds were monitored until day 35 postsurgery, when hypertrophic scar formation reached its peak. Dry wound weight, scar thickness, hypertrophic index (HI), and tissue cellularity of treated and untreated wounded tissue samples were evaluated as an index for scar formation. The results of this study showed that reepithelialized wounds treated with LIPO+IFN and to a lesser extent with LIPO alone were reduced in thickness, HI, and cellularity compared with untreated control wounds or LIPO+IFN-treated open wounds. Dry wound weight was also reduced but not significantly. The findings of this study suggest that LIPO+IFN is more effective than using LIPO alone in reducing the scar formation in a rabbit fibrotic ear model. Further investigation is required to confirm these results.


Genome Expression Balance in a Triploid Trihybrid Vertebrate.
Polyploidy is increasingly recognized as a driver of biological diversity. How and why polyploidization affects gene expression is critical to understanding the link between ploidy elevation and diversification. In polyploid plants, multiple studies have demonstrated that ploidy elevation can confer major but variable consequences for gene expression, ranging from gene-by-gene alterations to entirely silenced genomes. By contrast, animal polyploids remain largely uncharacterized. Accordingly, how animals respond to and manage polyploidy events is not understood. Here, we address this important knowledge gap by analyzing transcriptomes from a triploid hybrid animal, a unisexual Ambystoma salamander, and three sexual Ambystoma species that represent all three parental genomes in the unisexual. We used a novel bioinformatics pipeline that includes competitively mapping triploid sequences to a reference set of orthologous genes in the sexual species to evaluate subgenome expression. Our comparisons of gene expression levels across the three parental genomes revealed that the unisexual triploid displays a pattern of genome balance, where 72% of the genes analyzed were expressed equally among the subgenomes. This result is strikingly different from the genome imbalance typically observed in hybrid polyploid plants. Our analyses represent the first to address gene expression in a triploid hybrid animal and introduce a novel bioinformatic framework for analyzing transcriptomic data.


Environmental heterogeneity promotes spatial resilience of phototrophic biofilms in streambeds.
The loss of environmental heterogeneity threatens biodiversity and ecosystem functioning. It is therefore important to understand the relationship between environmental heterogeneity and spatial resilience as the capacity of ecological communities embedded in a landscape matrix to reorganize following disturbance. We experimented with phototrophic biofilms colonizing streambed landscapes differing in spatial heterogeneity and exposed to flow-induced disturbance. We show how streambed roughness and related features promote growth-related trait diversity and the recovery of biofilms towards carrying capacity (CC) and spatial resilience. At the scale of streambed landscapes, roughness and exposure to water flow promoted biofilm CC and growth trait diversity. Structural equation modelling identified roughness, post-disturbance biomass and a 'neighbourhood effect' to drive biofilm CC. Our findings suggest that the environment selecting for adaptive capacities prior to disturbance (that is, memory effects) and biofilm connectivity into spatial networks (that is, mobile links) contribute to the spatial resilience of biofilms in streambed landscapes. These findings are critical given the key functions biofilms fulfil in streams, now increasingly experiencing shifts in sedimentary and hydrological regimes.


Smooth lipopolysaccharide is the major protective antigen for mice in the surface extract from IATS serotype 6 contributing to the polyvalent Pseudomonas aeruginosa vaccine PEV.
The nature of the protective antigen in one of the sixteen monovalent extracts (viz., extract-6) contributing to the pseudomonas polyvalent extract vaccine (PEV) was studied in a mouse challenge assay. Selective removal, by filtration through Sep-Pak C18 cartridges, of two major protein antigens with molecular weights of 16,200 and 21,000 had no effect on the protection afforded by extract-6. When analyzed on the basis of 2-keto-3-deoxyoctonate, lipopolysaccharide (LPS) purified by hot phenol extraction (LPS-A) from Pseudomonas aeruginosa (International Antigenic Typing System serotype 6) could account in full for the protective capacity of extract-6. Comparative analysis of LPS heterogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining indicated that both extract-6 and LPS-A possessed similar spectra of smooth LPS molecules, containing between 10 and approximately equal to 50 O-antigen repeating units. Differences in the profiles of heterogeneity displayed by LPS in LPS-A and extract-6 were restricted to molecular species with short O-antigen chains. Subfractionation of LPS molecules on the basis of number of O-antigen repeating units was achieved by gel filtration in the presence of deoxycholate. Protection experiments performed on the subfractionated species of LPS-A revealed a relationship between O-antigen chain length and protective capacity; molecules with over 18 O-antigen repeating units being 50 to 100 times more protective than those with zero-two repeating units. The results indicate that most of the protection afforded by LPS-A and extract-6 can be accounted for by LPS molecules possessing extended (10 or more) O-antigen repeating units.


Is late-onset multiple sclerosis associated with a worse outcome?
To describe the characteristics of late-onset multiple sclerosis (MS) (LOMS, 50+ years) vs adult-onset MS (AOMS, 16 to <50 years) and examine prognosis and associated risk factors. Patients with definite MS, onset prior to July 1988, registered with a BCMS clinic before July 1998, with at least one Expanded Disability Status Scale (EDSS) score, were selected from the longitudinal population-based British Columbian (BC) MS database. Clinical and demographic characteristics were compared between LO and AOMS. Progression was measured as time to reach sustained EDSS 6 and potential risk factors examined were sex, disease course (primary progressive [PP] vs relapsing [R]), and onset symptoms. Of those eligible (n = 2,837), LOMS comprised 132 (4.7%), with PPMS predominating (54.5% vs 10.6% in AOMS, p < 0.0005). Motor onset symptoms were more prevalent in LOMS and sensory and optic neuropathy more prevalent in AOMS (p < 0.0005). AOMS averaged 27.7 years (95% CI: 26.3 to 29.1) to EDSS 6 from onset vs 16.9 years (95% CI: 9.0 to 24.8) in LOMS, p < 0.0005. However, AOMS was associated with a younger age at EDSS 6 (58.4 years [95% CI: 57.1 to 59.6] vs 71.2 years [95% CI: 65.2 to 77.3] in LOMS, p < 0.0005). There were no differences in progression between AO or LO for those with PPMS (p = 0.373) or R-MS (p = 0.438), although considerable variation was observed. Late-onset multiple sclerosis (LOMS) is not necessarily associated with a worse outcome: first, progression in the primary progressive or relapsing patients differed little between late-onset vs adult-onset; secondly, those with LOMS were older when reaching Expanded Disability Status Scale 6. The disease course has a far greater implication for disease prognosis than the presence of LOMS.


Cyst of the canal of Nuck: an atypical course with cyclic changing of size.
As the canal of Nuck normally obliterates before birth, a patent canal is a rare anatomic variant in adult women analogue to the patent processus vaginalis in men. In a patent canal of Nuck, pathologies such as hernias and cyst can build within time. Such cysts themselves are so uncommon that they are mostly described in case reports. Normally, cysts of the canal of Nuck present as a consistent, inguinal swelling with or without pain. Interestingly, in our case, the painful swelling was cyclic changing from the size of a plum to being clinically undetectable within the course of a day. To the best of our knowledge, this is the first description of such an unusual course. The cyst was removed operatively via an open approach. The spasms declined shortly after the operation. At 1 year postoperatively, the patient was still asymptomatic.


Comparison of static and flow cytofluorometry for estimation of DNA index and S-phase fraction in fresh and paraffin-embedded breast carcinoma tissue.
DNA index, S-phase and G2/M fractions were measured in breast carcinomas before and after paraffin-embedding. Unfixed tumors were analysed with flow cytometry, while cells prepared from fixed and paraffin-embedded tumors were analysed with both static cytometry and flow cytometry. Cells for static cytometry were prepared with pepsin and cells for flow cytometry were prepared with trypsin. In 44 of 51 paraffin-embedded tumors, analysed with flow cytometry, both DNA index and S-phase fraction could be estimated. There was a strong correlation between the three methods of obtaining DNA indices and S-phase fractions, but this was not true for G2/M fractions. Histograms from flow cytometry of archival material were corrected for background. We conclude that cells prepared from formalin-fixed and paraffin-embedded breast cancer tissue can yield reliable estimation of DNA index and S-phase fraction.


Horseradish peroxidase-catalyzed hydrogelation consuming enzyme-produced hydrogen peroxide in the presence of reducing sugars.
In the present work, three kinds of reducing sugars: glucose, galactose, and mannose, are applied to horseradish peroxidase (HRP)-catalyzed hydrogelation of an aqueous solution containing natural polymers modified with phenolic hydroxyl moieties. In this system, HRP consumes hydrogen peroxide that was generated from the oxidation of thiol groups in HRP in the presence of reducing sugars. Herein, we highlight the versatility of applicable sugar types and the controllable hydrogel properties. The mechanical properties and microstructures of the resultant hydrogels can be well controlled by varying the concentration and the reducing power of sugars. Moreover, reducing sugar-independent cytocompatibility of the hydrogels was confirmed by the growth of cells on them. The wide selection of sugar types provides a better understanding of the reaction mechanism and enables the characterization of hydrogels with well-controlled properties.


Bedside monitoring of respiratory function.
The primary focus of any monitoring technique is to alert the practitioner to change. Assessment, evaluation, and analysis of the data provide the basis for clinical decision-making. Monitoring spontaneous ventilatory parameters offers an overall assessment of the effectiveness of maintaining pulmonary gas exchange. Blood gas analysis provides the cornerstone for evaluating cardiopulmonary status and is an essential tool. The evaluation of dead space and shunt provides a foundation for differentiation between ventilation and perfusion mismatching. Collectively, these assessments focus on the stability of the cardiovascular and respiratory systems. Although modern technology is continually producing increasingly sophisticated methods of respiratory function monitoring, experienced observation by the clinician is still the key to successful assessment.


Determination of acetate and formate in vegetable oils by ion chromatography after multivariate optimization of the extraction process using a Doehlert design.
In this work, we present the development of a method for the determination of acetate and formate in vegetable oils by ion chromatography with conductometric detection following their extraction from samples using a diluted KOH solution. The extraction procedure was optimized using a multivariate approach. The application of a 24 full factorial design showed that the mass of sample, extraction time, and KOH concentration presented significant influence on the extraction of both acetate and formate, whereas the temperature presented little influence on the process. As a result, we set the extraction temperature at 22 °C and performed the multivariate optimization of the other variables using a Doehlert design. The optimum conditions were: 4.8 g of sample, 8 mmol L-1 KOH solution and 19 min extraction time. Six samples of vegetable oils (soybean, corn, canola, sunflower and olive) were analyzed and recovery tests provided recovery percentages in the range of 82-118%.


The role of reactive oxygen intermediates in nonspecific monocyte cytotoxicity induced by immune complexes.
Normal human monocytes were induced to lyse nonsensitized target cells when triggered by precipitating immune complexes (IC) or soluble heat-aggregated IgG (HAIgG). Catalase, azide, cyanide and three aminoacids employed as quenchers of ClO, significantly inhibited this nonspecific cytotoxicity (NSC), suggesting an important role for the myeloperoxidase (MPO) system. However, HO and/or 1O2 may also be involved in the lysis, since certain scavengers of these species such as mannitol, benzoate, ethanol and histidine, as well as superoxide dismutase (SOD), partially inhibited NSC. Moreover, cyanide and azide were unable to completely abrogate this lytic activity. When NSC was compared to antibody dependent cellular cytotoxicity (ADCC), it was found that neither catalase nor oxygen-species scavengers affected ADCC while azide and cyanide significantly enhanced it. Antibody-coated target cells were also destroyed by IC-triggered monocytes. However, kinetic analysis and studies on the capacity of catalase to inhibit the lysis demonstrated that it was mediated through a NSC-like mechanism. The cytotoxic system described in this report offers a suitable model to study in vitro alternative lytic mechanisms triggered through monocyte receptors for the Fc portion of IgG (Fc gamma R).


Pockets of short-range transient order and restricted topological heterogeneity in the guanidine-denatured state ensemble of GED of dynamin.
The nature and variety in the denatured state of a protein, a non-native state under a given set of conditions, has been a subject of intense debate. Here, using multidimensional NMR, we have characterized the 6 M Gdn-HCl-denatured state of GED, the assembly domain of dynamin. Even under such strongly denaturing conditions, we detected the presence of conformations in slow exchange on the NMR chemical shift time scale. Although the GED oligomer as well as the SDS-denatured monomeric GED were seen to be predominantly helical [Chugh et al. (2006) FEBS J. 273, 388-397], the 6 M Gdn-HCl-denatured GED has largely beta-structural preferences. However, against such a background, we could detect the presence of a population with a short helical stretch (Arg42-Ile47) in the ensemble. The 1H-1H NOEs suggested presence of pockets of transient short-range order along the chain. Put together these segments may lead to a rather small number of interconverting topologically distinguishable ensembles. Spectral density analysis of 15N relaxation rates and {1H}-15N NOE, measured at 600 and 800 MHz, and comparison of J(0) with hydrophobic patches calculated using AABUF approach, indicated presence of four domains of slow motions. These coincided to a large extent with those showing significant Rex. Additionally, a proline residue in the connection between two of these domains seems to cause a fast hinge motion. These observations help enhance our understanding of protein denatured states, and of folding concepts, in general.


Nuclear quadrupole hyperfine structure in the microwave spectrum of HCl-N2O: electric field gradient perturbation of N2O by HCl.
The microwave spectra of six isotopomers of HCl-N(2)O have been obtained in the 7-19 GHz region with a pulsed molecular beam, Fourier transform microwave spectrometer. The nuclear quadrupole hyperfine structure due to all quadrupolar nuclei is resolved and the spectra are analyzed using the Watson S-reduced Hamiltonian with the inclusion of nuclear quadrupole coupling interactions. The spectroscopic constants determined include rotational constants, quartic and sextic centrifugal distortion constants, and nuclear quadrupole coupling constants for each quadrupolar nucleus. Due to correlations of the structural parameters, the effective structure of the complex cannot be obtained by fitting to the spectroscopic constants of the six isotopomers. Instead, the parameters for each isotopomer are calculated from the A and C rotational constants and the chlorine nuclear quadrupole coupling constant along the a-axis, chi(aa). There are two possible structures; the one in which hydrogen of HCl interacts with the more electronegative oxygen of N(2)O is taken to represent the complex. The two subunits are approximately slipped parallel. For H (35)Cl-(14)N(2)O, the distance between the central nitrogen and chlorine is 3.5153 A and the N(2)O and HCl subunits form angles of 72.30 degrees and 119.44 degrees with this N-Cl axis, respectively. The chlorine and oxygen atoms occupy the opposite, obtuse vertices of the quadrilateral formed by O, central N, Cl, and H. Nuclear quadrupole coupling constants show that while the electric field gradient of the HCl subunit remains essentially unchanged upon complexation, there is electronic rearrangement about the two nitrogen nuclei in N(2)O.


Clinical Outcomes After Neurolysis for the Treatment of Peroneal Nerve Palsy: A Systematic Review and Meta-Analysis.
Neurolysis techniques have been adapted for decompression of peripheral nerves in multiple locations, including the common peroneal nerve (CPN) at the fibular neck. The aim of this study was to conduct a systematic review and meta-analysis to summarize the clinical outcomes of neurolysis for the management of peroneal nerve palsy (PNP). Preferred Reporting Systems for Systematic Reviews and Meta-Analyses guidelines were followed for this meta-analysis. Four databases were queried, and randomized clinical trials, cohort studies, case-control studies, and case series with n > 10 published in English that evaluated clinical outcomes of neurolysis for the treatment of PNP and foot drop were included. Two reviewers completed screening and data extraction. Methodological quality was evaluated using the Newcastle-Ottawa Scale. A total of 493 articles were identified through literature search. Title and abstract screening identified 39 studies for full-text screening. Ten articles met the inclusion criteria for qualitative analysis, and 8 had complete data for meta-analysis.Overall, there were 368 patients (370 nerves) who had neurolysis of the CPN for PNP, of which 59.2% (n = 218) were men and 40.8% (n = 150) were women. The mean age of the patients was 47.1 years (SD, 10.0 years), mean time to surgery was 9.65 months (SD, 6.3 months), and mean follow-up time was 28 months (SD, 14.0 months). The median preoperative Medical Research Council (MRC) score was 1 (IQR 0, 3), with 42.2% (n = 156) having MRC score of 0. The median postoperative MRC score was 5 (IQR 4, 5), with 53.9% (n = 199) having MRC score of 5. Complications of neurolysis of the peroneal nerve for treatment of PNP included postoperative infection (0.54%, n = 2), wound dehiscence (0.27%, n = 1), hematoma (0.54%, n = 2), bleeding (0.27%, n = 1), relapse of PNP (0.27%, n = 1), and 1 case of mortality due to sepsis. Our meta-analysis shows that neurolysis of the CPN is safe and improves ankle dorsiflexion strength in patients with PNP. Future studies should use a standardized method of measuring sensory outcomes, and studies of higher levels of evidence are needed to better assess the clinical outcomes of neurolysis for treatment of PNP.


Accelerate PhenoTestTM BC Kit Versus Conventional Methods for Identification and Antimicrobial Susceptibility Testing of Gram-Positive Bloodstream Isolates: Potential Implications for Antimicrobial Stewardship.
The Accelerate PhenoTestTM BC kit (AXDX) provides rapid organism identification (ID) and antimicrobial susceptibility testing (AST) results. Its potential role for antimicrobial stewardship is unknown. To compare the diagnostic accuracy of AXDX with conventional methods (CMs) and assess AXDX's potential role for antimicrobial stewardship in patients with Gram-positive bloodstream infections (BSIs). This retrospective cohort study included adults with Staphylococcus aureus or Enterococcus spp BSIs from July 2014 to January 2016 at a tertiary care medical center. Available isolates were tested on AXDX, and ID and AST results from AXDX were compared with those from CMs (VITEK 2 or ETEST). The following antibiotics were assessed for categorical agreement (CA) and essential agreement (EA) between the methods: ampicillin and daptomycin ( Enterococcus spp only), erythromycin and cefoxitin ( S aureus only), linezolid, and vancomycin. Potential role of AXDX for stewardship was assessed via a retrospective audit by infectious diseases clinicians. We included 231 patients with S aureus (n = 112) or Enterococcus spp (n = 119) BSIs, and 106 unique isolates were available for ID and AST performance analyses. Sensitivity and specificity of AXDX for ID were 98.0% and 99.5%, respectively. CA and EA for the tested antibiotics were >97%. In Monte Carlo simulations, AXDX coupled with stewardship personnel (either 24/7 or Monday to Friday) would have allowed unnecessary therapy to be stopped and active/targeted therapy to be started ≥24 hours sooner in >50% of patients. Compared with CMs, AXDX had similar diagnostic accuracy and can potentially optimize therapy sooner in patients with Gram-positive BSIs.


The Hsp90 inhibitor 17-allylamide-17-demethoxygeldanamycin induces apoptosis and differentiation of Kasumi-1 harboring the Asn822Lys KIT mutation and down-regulates KIT protein level.
Heat shock protein 90 (Hsp90) serves as a chaperone for a number of cell signaling proteins, including many tyrosine and serine/threonine kinases, which are involved in proliferation and/or survival. The benzoquinone ansamycin geldanamycin has been shown to bind to Hsp90 and to specifically inhibit this chaperone's function, resulting in client protein destabilization. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a chemical derivative of geldanamycin. KIT is the receptor for stem cell factor (SCF) and required for normal hematopoiesis. Mutations in c-Kit result in ligand-independent tyrosine kinase activity and uncontrolled cell proliferation. Kasumi-1 is t(8;21) acute myeloid leukemia (AML) cell line harboring mutated KIT with Asn822Lys substitution. Our present studies demonstrate that 17-AAG inhibits Kasumi-1 cells proliferation and exerts apoptosis- and differentiation-inducing effects in a dose- and time-dependent manner. The growth-inhibitory IC50 value for 17-AAG treatment is 0.62mumol/L. Characteristic apoptotic features were confirmed by morphology, internucleosomal DNA fragmentation, and annexin V staining. 17-AAG also causes the G0/G1 block of Kasumi-1 cells. Significantly, 17-AAG-induced apoptosis of Kasumi-1 cells is associated with a decline in KIT protein level. Our findings strongly suggest that 17-AAG might be an effective therapeutic agent targeting AML cells harboring mutated KIT.


Quantum Dynamics of the (18)O + (36)O2 Collision Process.
We report full quantum cross sections and rate constants for the (18)O + (36)O2 → (36)O2 + (18)O collision process. This constitutes to the best of our knowledge the first dynamical study of the (18)O(18)O(18)O system, with three identical (18)O oxygen atoms. We emphasize the comparison with the (16)O + (32)O2 collision as this latter presents the exact same features as the one treated here, except the consistent change of mass for all three atoms. We find very similar behaviors in the cross sections, and we confirm that the rates are faster when three identical nuclei are involved. In particular, we cannot dynamically study this system with classical trajectory methods, and we have to include properly the indistinguishability of the three (18)O nuclei; however, we note some slight differences with the (16)O(16)O(16)O benchmark system, and we focus our analysis on their origin.


Decoding the mechanical conductance switching behaviors of dipyridyl molecular junctions.
Dipyridyl molecular junctions often show intriguing conductance switching behaviors with mechanical modulations, but the mechanisms are still not completely revealed. By applying the ab initio-based adiabatic simulation method, the configuration evolution and electron transport properties of dipyridyl molecular junctions in stretching and compressing processes are systematically investigated. The numerical results reveal that the dipyridyl molecular junctions tend to form specific contact configurations during formation processes. In small electrode gaps, the pyridyls almost vertically adsorb on the second Au layers of the tip electrodes by pushing the top Au atoms aside. These specific contact configurations result in stronger molecule-electrode couplings and larger electronic incident cross-sectional areas, which consequently lead to large breaking forces and high conductance. On further elongating the molecular junctions, the pyridyls shift to the top Au atoms of the tip electrodes. The additional scattering of the top Au atoms dramatically decreases the conductance and switches the molecular junctions to the lower conductive states. Perfect cyclical conductance switches are obtained as observed in the experiments by repeatedly stretching and compressing the molecular junctions. The O atom in the side-group tends to hinder the pyridyl from adsorbing on the second Au layer and further inhibits the conductance switch of the dipyridyl molecular junction.


Common genital complaints in women: the contribution of psychosocial and infectious factors in a population-based cohort study in Goa, India.
The genital complaint of abnormal vaginal discharge is common in South Asia. We describe the risk factors for the incidence of the complaint in women of reproductive age. Method Population-based cohort study in Goa, India. Out of 3000 randomly selected women, 2494 women participated. The outcome was an incident case of the complaint of abnormal vaginal discharge at 6 months (T1) and 12 months (T2) review. In total 71 (3.6%, 95% CI 2.8-4.5%) of the 2000 eligible women reviewed at T1 reported the complaint; and 80 (4.0%, CI 3.2-5.0%) of the 1999 women who did not complain of abnormal vaginal discharge at T1 reported it at T2. Multivariate logistic regression analysis identified the following factors as associated with the complaint: younger age (OR 0.26, CI 0.1-0.5 for women aged 40-49 years compared with women aged 18-24 years); illiteracy (OR 1.48, CI 0.9-2.4); religion (Muslim women OR 3.15, CI 1.7-6.0 compared with Hindu women); women's concerns regarding their spouse's extramarital relationships (OR 3.46, CI 1.2-10.0); current BV infection (OR 1.87, CI 1.2-2.9); somatoform complaints (OR 3.30, CI 1.7-6.5 for the highest somatoform score quartile compared with the lowest); and depression and anxiety (OR 1.55, CI 0.9-2.6 for the highest mental health score quartile compared with the lowest). Reproductive and sexual health programmes must strengthen the capacity of practitioners to assess and treat bacterial vaginosis and psychosocial problems in women with complaints of abnormal vaginal discharge.


[Acrylic bone cement use for internal spondylodesis in neurosurgical operations].
Vertebral column stabilization relying on performing of surgical internal spondylodesis with acrylic bone cement (methylmethacrylate, MMA) was carried out in 27 cases treated surgically in Department and Clinic of Neurosurgery in Poznań from 1996 to 1999. The age of patients was 16-69 (mean age 50.29 +/- 15.29) years. Male patients predominated (2:1). The vertebral lesion was caused by neoplasm (55% of cases), degenerative disease (26%), trauma (19%). Pathological changes were found in cervical region in 16 (59%), in thoracic region in 6 (22%) and in lumbar region in 5 (19%) patients. The anterior surgical approach to vertebral column was chosen in 17 (63%), posterolateral approach in 8 (30%) and posterior approach in 2 (7%) patients. Bone acrylic cement was used for reconstruction of vertebral body damaged by neoplasm or trauma, whereas it substituted the removed intervertebral disc or vertebral body in degenerative diseases. The acrylic cement graft in all cases maintained the proper anterior and medial vertebral column alignment. Semiliquid acrylic cement was used for filling of defects after tumour removal in thoracic and lumbar vertebral bodies. Acrylic cement graft was properly prepared in cuboid form and was inserted into the intervertebral spaces in patients with trauma or degenerative diseases. In all cases involving bone acrylic cement, stabilization of the vertebral segment was completed by metallic implants (cervical plates, "Z" plates, intrapedicular screws and rods). No postoperative complications (wound infections or implant dislocation) were observed. Postoperative, neurological signs were intensified in 3 cases (12%) and were regressive. Mortality rate was 4%. This type of internal spondylodesis makes possible to restore the anterior and medial columns and immobilisation of the proper vertebral segments.


[Active teaching-learning methodologies in health education: current debates].
The vertiginous transformations of the contemporary societies have been raising questions concerning aspects of professional education. Such questions have been raised in a more and more incisive way. This debate gains a new shape when applied to health work, where theory and practice cannot be dissociated, and where the development of an integral vision of the human being and the amplification of the concept care are essential for a proper performance. Based on these considerations, this article aims to discuss the main methodological transformations in the education process of health professionals, with emphasis to active teaching-learning methodologies.


Peripheral inflammatory biomarkers and risk of Parkinson's disease.
Experimental and postmortem evidence indicates a role of neuroinflammation in the pathogenesis of Parkinson's disease. The authors prospectively examined whether plasma concentrations of inflammatory biomarkers assessed before Parkinson's disease diagnosis were predictive of future risk of the disease in a nested case-control study in the United States (1993-2002), including 84 incident cases and 165 matched controls. Blood was collected from patients on average 4.3 years before the diagnosis. After adjustment for potential confounders, higher level of interleukin-6 was associated with a greater risk of Parkinson's disease. Compared with the lowest quintile, the odds ratios were 1.5 for the second, 1.6 for the third, 2.7 for the fourth, and 3.4 for the fifth quintiles (p for trend = 0.03). In contrast, concentrations of other inflammatory biomarkers including C-reactive protein, fibrinogen, and tumor necrosis factor-alpha receptors were not related to the risk. These data suggest that men with high plasma concentrations of interleukin-6 have an increased risk of developing Parkinson's disease. However, this finding should be interpreted with caution because of the small sample size and the lack of associations with other biomarkers of inflammation.


Long-term Safety of Directly Discharging Patients Home from the ICU Compared to Ward Transfer.
Purpose: To evaluate the long-term safety of directly discharging intensive care unit (ICU) survivors to their home. Methods: A retrospective observational cohort of 341 ICU survivors who were directly discharged home from the ICU ("direct discharge") or discharged home ≤72 hours after ICU transfer to the ward ("ward transfer") was conducted in Regina, Saskatchewan ICUs between September 1, 2016 and September 30, 2018. The primary outcome was 90-day hospital readmission. Secondary outcomes included 30-day, 90-day, and 365-day emergency department (ED) visits, 30-day and 365-day hospital readmissions, and 365-day mortality. All outcomes were evaluated by multivariable Cox regression after adjustment for demographic and clinical characteristics. Results: Of 341 survivors (25.5% of total ICU visits), 148 (43.4%) patients were direct discharges and 193 (56.6%) were ward transfers. The median age was 46 years (interquartile range, 34-62), 38.4% were female, and 61.8% resided in Regina. Compared to the ward transfer cohort, more patients in the direct discharge cohort had at least one 90-day hospital readmission (30.4% versus 17.1% of patients, adjusted hazard ratio 2.09, 95% confidence interval 1.28-3.40, P = .003), after adjustment. Additionally, there were more 90-day ED visits (P = .045), and 30-day (P = .049) and 365-day hospital readmissions (P = .03), after adjustment. Conclusions: In Saskatchewan, direct discharge compared to ward transfer was associated with an increase in 90-day hospital readmissions, and potentially other clinical outcomes. Further study is necessary.


Ribosomal synthesis of polypeptoids and peptoid-peptide hybrids.
Here we report a new methodology for mRNA-programmed synthesis of peptoids and peptoid-peptide hybrids by means of translation machinery under the reprogrammed genetic code. We initially screened N-substituted glycines (rGly) for their single incorporation into a nascent peptide chain and found translation machinery accepts a variety of rGly for elongation. Moreover, we have shown consecutive elongations of rGly and mRNA-directed synthesis of cyclic peptoid-peptide hybrids. This methodology offers a powerful tool for mRNA-programmed library synthesis of peptoids and peptoid-peptide hybrids with linear and cyclic scaffolds, potentially leading to the discovery of drug candidates with proteolytic stability and membrane permeability.


IFITM3 Rs12252-C Variant Increases Potential Risk for Severe Influenza Virus Infection in Chinese Population.
Background: Interferon Inducible Transmembrane 3 (IFITM3) is a key factor in interferon pathway and it involves host's immune response against multiple viruses. IFITM3 rs12252-C was associated with severe influenza virus infection in several studies, however whether this association is universal to all types of influenza virus or diverse ethnic populations remain controversial. Method: A case-control genetic association study was performed from September 2013 to April 2014 and September 2014 to April 2015. All samples were tested for influenza using RT-PCR, and genotyped by High Resolution Melting assay. Results: A total of 65 healthy people, 165 mild influenza-like illness (ILI) cases and 315 severe acute respiratory infection (SARI) cases were enrolled in this study. The frequency of CC genotype was much higher in SARI cases with IVI than that in ILI cases with IVI (61.59 vs. 27.16%), leading a 4.67-fold greater risk for severe IVI than other two genotypes. Moreover, the risk of IFITM3 rs12252-C variant for severe IVI was specific for both influenza A and influenza B. Conclusion:IFITM3 rs12252 CC genotype was associated with severity rather than susceptibility of IVI in Chinese population, and this strong effect was observed in all subtypes of seasonal influenza infection.


Accuracy and efficiency of electronic energies from systematic molecular fragmentation.
A systematic method for approximating the ab initio electronic energy of molecules from the energies of molecular fragments is tested on a large sample of typical organic molecular structures. The detailed methods, including some additional refinements for molecular rings and long range interactions, are described. The accuracy and computational efficiency of the systematic hierarchy of methods are reported.


On the association of restriction fragment length polymorphisms across species boundaries.
We study the expected values of gametic-phase disequilibrium in both nuclear and cytonuclear systems in a finite population composed of reproductively isolated subpopulations. Random drift alone within each subpopulation will generate permanent overall non-zero gametic-phase disequilibrium in both a two-locus nuclear system and a cytonuclear system unless the population has an overall initial disequilibrium of zero. We derive formulae for the expected overall disequilibrium when mutation is involved and demonstrate that these values decay to zero at an extremely slow rate compared with the decay of the expected disequilibria within each subpopulation.


[Synthetic drugs consumed at "rave parties"].
Significant health risks result from the rising consumption of psychoactive drugs employed for festive objectives. Once alerted by this new danger, the French interministerial mission for the fight against illicit drugs and drug abuse (MILDT) set up a system of chemical and social studies in collaboration with the European Office of Drugs and Drug Abuse. The goal of the project is to discover the chemical structure of currently used drugs, and to study and predict their pharmaco-toxicaological effects. Over the last five Years, the laboratory of the Fernand Widal Hospital has analyzed more than 2,000 samples: 181 different molecules have been identified, ranging from inoffensive agents to very active drugs, including some misused licit drugs. Many of the compounds identified are amphetamine derivatives. The most widespread drug was ecstasy. Consumers and dealers seek substances with more potent psycho-stimulating effects which are not on the narcotics list and less expensive, producing effects as close to ecstasy as possible. In this extremely permissive context, other non-amphetaminic products are in circulation, including anesthesics such as ketamine and CHB, leading users to unconscious assent. The medical risks increase even more when several psychoactive substances are consumed in combination.


[The consolidation of memory, one century on].
The theory of memory consolidation, based on the work published by Georg Elias Muller and Alfons Pilzecker over a century ago, continues to guide research into the neurobiology of memory, either directly or indirectly. In their classic monographic work, they concluded that fixing memory requires the passage of time (consolidation) and that memory is vulnerable during this period of consolidation, as symptoms of amnesia appear when brain functioning is interfered with before the consolidation process is completed. Most of the experimental data concerning this phenomenon strongly support the theory. In this article we present a review of experiments that have made it possible to put forward a model that explains the amnesia produced in conventional learning conditions, as well as another model related to the protection of memory when the same instances of learning are submitted to a situation involving intensive training. Findings from relatively recent studies have shown that treatments that typically produce amnesia when they are administered immediately after a learning experience (during the period in which the memory would be consolidating itself) no longer have any effect when the instances of learning involve a relatively large number of trials or training sessions, or relatively high intensity aversive events. These results are not congruent with the prevailing theories about consolidation.


New chemistry from natural product biosynthesis.
Catalysts are a vital part of synthetic chemistry. However, there are still many important reactions for which catalysts have not been developed. The use of enzymes as biocatalysts for synthetic chemistry is growing in importance due to the drive towards sustainable methods for producing both bulk chemicals and high value compounds such as pharmaceuticals, and due to the ability of enzymes to catalyse chemical reactions with excellent stereoselectivity and regioselectivity. Such challenging transformations are a common feature of natural product biosynthetic pathways. In this mini-review, we discuss the potential to use biosynthetic pathways as a starting point for biocatalyst discovery. We introduce the reader to natural product assembly and tailoring, then focus on four classes of enzyme that catalyse C─H bond activation reactions to functionalize biosynthetic precursors. Finally, we briefly discuss the challenges involved in novel enzyme discovery.


Distinct regulators for Plk1 activation in starfish meiotic and early embryonic cycles.
The Polo-like kinase, Plk, has multiple roles in regulating mitosis. In particular, Plk1 has been postulated to function as a trigger kinase that phosphorylates and activates Cdc25C prior to the activation of cyclin B-Cdc2 and thereby initiates its activation. However, the upstream regulation of Plk1 activation remains unclear. Here we have studied the interplay between Plk1 and Cdc2 through meiotic and early embryonic cycles in starfish. Distinct kinases, cyclin B-Cdc2, MAPK along with cyclin B- and/or cyclin A-Cdc2 and cyclin A-Cdc2, were unique upstream regulators for Plk1 activation at meiosis I, meiosis II and embryonic M-phase, respectively, indicating that Plk1 is not the trigger kinase at meiotic reinitiation. When Plk1 was required for cyclin B-Cdc2 activation, the action of Plk1 was mediated primarily through suppression of Myt1 rather than through activation of Cdc25. We propose that Plk1 can be activated by either cyclin A- or cyclin B-Cdc2, and its primary target is Myt1.


Bovine Doppel (Dpl) and prion protein (PrP) expression on lymphoid tissue and circulating leukocytes.
Doppel (Dpl) protein shares some structural features with prion protein (PrP), whose pathologic isoform (PrPsc) is considered to be the causative agent of transmissible spongiform encephalopathies. Dpl is mainly expressed in testes but, when ectopically expressed in the central nervous system, is neurotoxic. We have examined the expression pattern of Dpl and PrP on bovine lymphoid tissues and circulating leukocytes. A polyclonal anti-Dpl antibody along with a panel of monoclonal antibodies specific for leukocyte membrane antigens or PrP were used to examine frozen sections from spleen, lymph nodes, and bone marrow by immunohistochemistry. Blood was analyzed by flow cytometry. Double staining was used to study the possible coexpression of the two proteins and to characterize cells expressing Dpl and/or PrP. Dpl was expressed in B-cells, in dendritic cells within lymphoid follicles, bone marrow, circulating myeloid cells, and circulating B-cells. The distribution of Dpl was quite similar to that of PrP. The only differences in expression observed concerned the low number of Dpl+ cells in lymph nodes and the strong Dpl positivity of circulating granulocytes. The two proteins were rarely co-expressed, suggesting an independent expression mechanism in resting cells. The role of Dpl+ leukocytes in the pathogenesis of Dpl- or PrP-induced diseases merits further investigation.


Inhibition of Phosphate-Induced Vascular Smooth Muscle Cell Osteo-/Chondrogenic Signaling and Calcification by Bafilomycin A1 and Methylamine.
Excessive phosphate concentrations trigger vascular calcification, an active process promoted by osteoinduction of vascular smooth muscle cells (VSMCs) with increased expression and activity of transcription factor RUNX2 (Core-binding factor α1, CBFA1), alkaline phosphatase (ALPL), TGFß1, transcription factor NFAT5, and NFAT5-sensitive transcription factor SOX9. The osteoinductive signaling and vascular calcification of hyperphosphatemic klotho-hypomorphic mice could be reversed by treatment with NH4Cl, effects involving decrease of TGFß1 and inhibition of NFAT5-dependent osteoinductive signaling. Known effects of NH4Cl include alkalinization of acidic cellular compartments. The present study explored whether osteo-/chondrogenic signaling could be influenced by alkalinization of acidic cellular compartments following inhibition of the vacuolar H+ ATPase with bafilomycin A1 or following dissipation of the pH gradient across the membranes of acidic cellular compartments with methylamine. Primary human aortic smooth muscle cells (HAoSMCs) were treated with high phosphate to trigger osteo-/chondrogenic signaling and calcification in the absence or presence of bafilomycin A1 or methylamine. Calcium content was determined using a QuantiChrom Calcium assay, ALP activity by a colorimetric assay and transcript levels by quantitative RT-PCR. High phosphate increased significantly the calcium deposition, CBFA1 and ALPL mRNA expression as well as alkaline phosphatase activity in HAoSMCs, all effects ameliorated by both, bafilomycin A1 and methylamine. High phosphate further significantly up-regulated the mRNA levels of TGFB1, NFAT5 and SOX9, effects significantly blunted by additional treatment with bafilomycin A1 or methylamine. Treatment of HAoSMCs with human TGFß1 protein or high phosphate up-regulated NFAT5, SOX9, CBFA1 and ALPL mRNA expression to similarly high levels which could not be further increased by combined treatment with high phosphate and TGFß1. Bafilomycin A1 failed to reverse the osteo-/chondrogenic signaling triggered by high phosphate together with TGFß1. Inhibition of the vacuolar H+ ATPase or dissipation of the pH gradient across the membranes of acidic cellular compartments both disrupt osteo-/chondrogenic signaling and calcium deposition in VSMCs, observations supporting the hypothesis that vascular calcification requires acidic cellular compartments.


Comparison of Temperamental Features, Anxiety, and Depression Levels Between Non-Cardiac Angina and Acute Coronary Syndrome.
In many studies that are aimed to determine the psychological profile of patients admitted to the emergency unit with non-cardiac angina (NCA), it was indicated that psychiatric problems, less effective problem-solving, and alexithymia are more common in NCA compared with acute coronary syndrome (ACS) patients. In this study, aiming to find predictive psychological clinical features, we compared the temperament, anxiety, and depression scores of patients with NCA and ACS. Sociodemographic variables of 63 patients (n=41 NCA, n=22 ACS) who were admitted to the emergency unit with chest pain were recorded. TEMPS-A scale was used for defining temperamental features, and Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression levels of patients in both groups. Sociodemographic variables and TEMPS-A and HADS scores were compared with χ2 and independent-groups t-test between the NCA and ACS groups. The NCA and ACS groups were similar in terms of sociodemographic variables. There was no statistical difference between groups in HDS (p=.12) and HAS (p=.39) scores and TEMPS-A scale depressive (p=.41), cyclothymic (p=.08), hyperthymic (p=.06), and anxious (p=.29) temperament scores. But, irritable temperament scores were significantly higher in the NCS group (p=.04). We believe that our findings will provide a basis for further studies in the diagnosis and treatment of NCA by contributing to the definition of NCA patients' psychological profiles.


[Association between epicardial fat volume and coronary artery calcification in patients with chronic kidney disease].
Objective: To evaluate whether epicardial fat volume (EFV) is related to coronary artery calcification in patients with chronic kidney disease(CKD). Method: Multi-slice computed tomography was performed in 30 healthy subjects and 120 patients with CKD. Cross-sectional tomographic cardiac slices from base to apex were traced semi-automatically using a Volume Viewer of AW4.3 off-line workstation, and EFV was measured by assigning Hounsfield units ranging from -250 to -30 HU to fat.The coronary artery calcification score was assessed by CaScoring software. High density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C) and collecting the body mass index (BMI), dialysis route, history of diabetes and coronary artery disease were used to analyze the relationship between EFV and other risk factors in patients with CKD. Results: There were 60.8%(73/120) male (mean age 62.8 years) and 39.2%(47/120) female (mean age 66.6 years) in the patients cohort, 73.3%(88/120) patients had coronary artery disease, 55.8%(67/120) had diabetes, 21 patients were on peritoneal dialysis and 9 on hemodialysis. EFV was apparently higher in stage 4-5 D CKD group compared with the control group((140.03±54.71), (145.01±64.56)and (141.45±62.04) cm(3) vs.(92.42±39.56)cm(3), P=0.007, 0.015 and 0.001), was similar between CKD3 and control group, and EFV was significantly higher in peritoneal dialysis group than in hemodialysis group and in coronary artery disease group compared with no coronary artery disease group((140.67±70.31) cm(3) vs.(105.22±61.49) cm(3), P=0.002). EFV was obviously higher in diabetes group than no diabetes group((148.41±65.78) cm(3) vs.(110.53±62.37) cm(3), P=0.007). CACS was apparently increased in stage 3-5 CKD group compared with the control group(140.0 vs.4.3, P<0.001). (3)When the patients were divided into four groups according to the eGFR, EFV was positively associated with CACS(r(s)=0.539, P=0.004) in control group, and the association become more robust in patients with CKD5(r(s)=0.841, P<0.000 1). EFV was related to age(r=0.662, P=0.005), BMI(r=0.648, P=0.009)and HDL-C(r=-0.433, P=0.024), but not related to eGFR and LDL-C. EFV was related to CACS(r=0.427, R(2)=0.182 3, P<0.001). CACS was positively correlated to age and BMI (all P<0.05)and negatively correlated with eGFR(P<0.05). Conclusions: Measurement of EFV may provide another useful noninvasive indicator of coronary artery calcification in CKD patients.


Metformin Exposure During Pregnancy and Lactation Did Not Cause Vascular Reactivity Alteration in Adult Male Offsprings.
Metformin has been used for the treatment of some metabolic diseases during gestation and the beneficial effects of metformin to the vascular system have been described in diabetic and obese animal models. Nevertheless, the long-term consequences to the vascular system of offsprings maternally exposed to metformin have not yet been characterized. Therefore, we want to test the hypothesis that gestational and lactational exposure to metformin would be safe for the vascular reactivity of male adult offsprings. Wistar female rats were treated with metformin 293 mg·kg·d, by gavage, from gestational day (GD) 0 to GD 21 (METG) or GD 0 until postnatal day 21 (METGL). Control dams received water by gavage in the same periods (CTRG and CTRGL). In male offsprings (75 days), the aortic reactivity to phenylephrine, acetylcholine, and sodium nitroprusside in the presence or absence of endothelium were evaluated. The results demonstrated that aortic contraction and relaxation were similar between groups. These data showed that metformin exposure during pregnancy and lactation did not interfere with aortic reactivity, suggesting that metformin exposure during gestational and lactation are safe for the offsprings' vascular system.


Human skeletal muscle size with ultrasound imaging: a comprehensive review.
Skeletal muscle size is an important factor in assessing adaptation to exercise training and detraining, athletic performance, age-associated atrophy and mobility decline, clinical conditions associated with cachexia, and overall skeletal muscle health. Magnetic resonance (MR) imaging and computed tomography (CT) are widely accepted as the gold standard methods for skeletal muscle size quantification. However, it is not always feasible to use these methods (e.g., field studies, bedside studies, and large cohort studies). Ultrasound has been available for skeletal muscle examination for more than 50 years and the development, utility, and validity of ultrasound imaging are underappreciated. It is now possible to use ultrasound in situations where MR and CT imaging are not suitable. This review provides a comprehensive summary of ultrasound imaging and human skeletal muscle size assessment. Since the first study in 1968, more than 600 articles have used ultrasound to examine the cross-sectional area and/or volume of 107 different skeletal muscles in more than 27,500 subjects of various ages, health status, and fitness conditions. Data from these studies, supported by decades of technological developments, collectively show that ultrasonography is a valid tool for skeletal muscle size quantification. Considering the wide-ranging connections between human health and function and skeletal muscle mass, the utility of ultrasound imaging will allow it to be employed in research investigations and clinical practice in ways not previously appreciated or considered.


[Placenta praevia percreta with bladder invasion: a life-threatening pregnancy complication].
Placenta percreta is characterized by the penetration of trophoblast through the myometrium and peritoneum. This invasion may also involve adjacent structures. This condition is the most serious of placental implantation anomalies. It is a rare but life-threatening complication of pregnancy. We present a case of placenta praevia percreta with involvement of the bladder, discuss the particularities of the diagnosis and management, and review the literature.


[Subcutaneous avulsion of the flexor digitorum profundus and flexor digitorum superficialis tendons of the ring and little fingers caused by blast injury].
The authors report a case of subcutaneous avulsion of flexor profundus and flexor superficialis tendons of the ring and little finger, caused by a blast injury. Treatment consisted of excision of the flexor superficialis tendon with transosseous reinsertion of the flexor profundus tendon. The functional result was good. Subcutaneous traumatic rupture of flexor tendons occurs infrequently, but simultaneous rupture of both flexor tendons is extremely rare. Knowledge of the subject is limited and treatment of this disorder is poorly defined.


Simultaneous assay for megakaryocyte colony-stimulating factor and megakaryocyte potentiator and its application.
We have devised a simultaneous assay system for megakaryocyte colony-stimulating factor (Meg-CSF) and megakaryocyte potentiator (Meg-Pot) by modifying a quantitative measuring technique for acetylcholinesterase activity (Ach-E) of megakaryocytes by automatic colorimetry using microplates. We cultured murine bone marrow cells treated with diisopropyl fluorophosphate in a serum-free system with serum-free pokeweek mitogen-stimulated spleen cell conditioned medium (PWM-SCM) and an unknown factor, preparing two microplates with the identical culture system. In the first plate, the total number of Ach-E-positive cells induced solely by the factor tested was indicative of Meg-CSF activity and additive increases in this parameter on simultaneous addition of PWM-SCM and the factor tested were indicative of early Meg-Pot activity. Total Ach-E activity (total change at optical density of 414 nm) per well was measured in the second plate to calculate total change at optical density of 414 nm per megakaryocyte, an indicator of late Meg-Pot activity. With this system, recombinant human erythropoietin showed both Meg-CSF and early and late Meg-Pot activities in in vitro megakaryopoiesis. Recombinant murine granulocyte-macrophage colony-stimulating factor possessed weak Meg-CSF and early Meg-Pot activity, whereas recombinant human granulocyte colony-stimulating factor exhibited late Meg-Pot activity and thrombocytopenic serum exhibited early and late Meg-Pot activities. This assay system is useful in screening Meg-CSF or Meg-Pot activities in unknown factors.


Development of scales measuring the capacity of community-based initiatives.
This article describes the development of two measures for the capacity of local public health initiatives. Data obtained from a qualitative study of eight community-based initiatives served as the basis for the development of a survey instrument. It was administered to a national sample of both leaders and nonleaders of 291 such initiatives. Because survey results for leaders and nonleaders differed, results could not be combined into a single data set for analysis. Results for each data set were analyzed by employing exploratory principal components and factor analyses. A 44-item, six-factor scale resulted for leaders and a 38-item, five-factor scale resulted for nonleaders. The high degree of overlap (22 items) between the two scales resulted in a combined 60-item instrument that can be administered to both leaders and nonleaders but analyzed separately.


[Densitometric evaluation of angiocinematographic x-ray films in cerebrovascular diseases (author's transl)].
21 patients suffering from cerebrovascular diseases were examined by means of angiocinematography. The 37 X-ray films were taken under standardized conditions of exposure and development, and were evaluated by use of densitometry. The flow speed and the blood volume/min were measured in the internal carotid artery, as well as the arterial transit time from the carotid siphon to standardized measuring points in the three branch groups of the middle cerebral artery. The haemodynamic parameters obtained from the clinically affected hemispheres or branch groups were compared with those obtained from the clinically non-affected. The aim of this study was to attempt to make a contribution towards the understanding of haemodynamic changes in connection with cerebrovascular diseases.